Adaptation to persistent neural input is a fundamental component of neural computation. Persistent neural activity in neurons within a sensory system can be caused both by a constant sensory stimulus and by intrinsic cellular factors, which are independent of sensory stimuli. While adapting to a persistent sensory stimulus could help a neuron adapt to its sensory environment, adapting to intrinsic properties could substantially limit the sensitivity of the sensory system to weak stimuli. Thus, understanding how neurons adapt to both stimulus-induced and intrinsic persistent activity is critical to understanding how sensory systems process information across a large range of sensory environments and delineating the factors that limit neural processing. Few studies have addressed these issues clearly because it requires access to multiple levels of an intact neural circuit and ability to manipulate both stimulus-induced and intrinsic persistent activity. The Drosophila olfactory system provides a unique opportunity to resolve these issues. This model organism provides experimental access to the first two stages of the olfactory system, the olfactory receptor neurons (ORNs) and the projection neurons (PNs), as well as the ability to control persistent activity in the ORNs. Stimulus-induced persistent ORN activity can be driven by a constant odor stimulus and control of the intrinsic ORN activity is provided by the inherent structure of the Drosophila olfactory system. ORNs span a large range of intrinsic activity, with some only generating 1 spike/sec while others generate 32 spikes/sec, and a specific PN only receive input from ORNs with the same level of intrinsic activity. Further, established fly genetic allow even more precise control of intrinsic activity. Activity of ORNs and PNs can be measured using electrophysiology and specific cells can be targeted using known maps of fly anatomy and genetic labeling of neurons with green fluorescent protein. In Specific Aim 1 we will compare how PNs signal brief ORN odor responses during increasing odor-induced persistent activity from the ORN. In Specific Aim 2 we will compare how PNs signal brief ORN odor responses across PNs that receive input from ORNs with a range of intrinsic activity. Additionally, in Aim 2 we will evaluate if PNs adapt to odor-induced persistent activity differently than intrinsic persistent activity. In Specific Aim 3 we will test how the adaptation observed in Aims 1 and 2 depend on known biological mechanisms. Insight gained from these studies into how downstream neurons adapt to changes in their persistent input and how that adaptation depends on the source of the persistent activity will help generate accurate models of how the neural system processes sensory stimuli and identify the factors that can limit sensory processing.